Suchergebnisse

Network science has long been recognized as a well-established discipline across many biological domains. In the particular case of cancer genomics, network discovery is challenged by the multitude of available high-dimensional heterogeneous views of data. Glioblastoma (GBM) is an example of such a complex and heterogeneous disease that can be tackled by network science. Identifying the architecture of molecular GBM networks is essential to understanding the information flow and better informing drug development and pre-clinical studies. Here, we review network-based strategies that have been used in the study of GBM, along with the available software implementations for reproducibility and further testing on newly coming datasets. Promising results have been obtained from both bulk and single-cell GBM data, placing network discovery at the forefront of developing a molecularly-informed-based personalized medicine. ; This work was partially supported by national funds through Fundação para a Ciência e a Tecnologia (FCT) with references CEECINST/00102/2018, CEECIND/00072/2018 and PD/BDE/143154/2019, UIDB/04516/2020, UIDB/00297/2020, UIDB/50021/2020, UIDB/50022/2020, UIDB/50026/2020, UIDP/50026/2020, NORTE-01-0145-FEDER-000013, and NORTE-01-0145-FEDER000023 and projects PTDC/CCI-BIO/4180/2020 and DSAIPA/DS/0026/2019. This project has received funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 951970 (OLISSIPO ...

Although it is well established that tumor-associated macrophages take part in each step of cancer progression, less is known about the distinct role of the so-called metastasis-associated macrophages (MAMs) at the metastatic site. Previous studies reported that Caveolin-1 (Cav1) has both tumor-promoting and tumor-suppressive functions. However, the role of Cav1 in bone-marrow-derived cells is unknown. Here, we describe Cav1 as an anti-metastatic regulator in mouse models of lung and breast cancer pulmonary metastasis. Among all the recruited inflammatory cell populations, we show that MAMs uniquely express abundant levels of Cav1. Using clodronate depletion of macrophages, we demonstrate that macrophage Cav1 signaling is critical for metastasis and not for primary tumor growth. In particular, Cav1 inhibition does not affect MAM recruitment to the metastatic site but, in turn, favors angiogenesis. We describe a mechanism by which Cav1 in MAMs specifically restrains vascular endothelial growth factor A/vascular endothelial growth factor receptor 1 (VEGF-A/VEGFR1) signaling and its downstream effectors, matrix metallopeptidase 9 (MMP9) and colony-stimulating factor 1 (CSF1). ; FWO-Strategic Basic Research (SB) doctoral fellowship (1S26917N), G.D.C. by a Pegasus FWO-Marie Curie fellowship (12114113N), A.I.O. by FCT Portugal (SFRH/BD/52287/2013), and M.E. by the DFG (EH 472/1-1) and Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society (2016/10538/2453). B.M.C. was funded by FCT Portugal (IF/00601/2012). M.M. received an ERC starting grant (OxyMO, 308459) and long-term structural Methusalem funding by the Flemish government (METH.14.08) ...

Epidermal growthf actor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61in glioma susceptibility and prognosis. Experimental Design:A case-control study involving197 glioma patients and 570 controlswas done. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). False-positive report probability was also assessed.The luciferase reporter gene assay was used to ascertain the functional consequences of this polymorphism. Results: Corroborating the univariate analysis, the multivariate model showed that the G allele conferred higher risks for gliomas (OR,1.32; 95% CI,1.04-1.67), glioblastomas (OR,1.47; 95% CI, 1.02-2.10), and oligodendrogliomas (OR,1.55; 95% CI,1.07-2.23).TheGG genotypeswere associatedwithincreased risk for gliomas (OR,1.71; 95%CI,1.07-2.73), glioblastomas (OR, 2.03; 95% CI, 1.02-4.05), and oligodendrogliomas (OR, 2.72; 95% CI, 1.18-6.28). In addition, the AG+GG genotypes were associated withhigher risk for gliomas (OR,1.52; 95% CI,1.03-2.23) and oligodendrogliomas (OR, 2.80; 95% CI,1.35-5.79). No significant associationwas observed between the EGF+61polymorphism and glioblastoma or oligodendroglioma patients'overall survival. The luciferase reporter gene assay exhibited a significant increased promoter activity for the G variant compared withthe referenceA allele. Conclusions: These findings support the role of the EGF+61polymorphism as a susceptibility factor for development of gliomas and show its implication on EGF promoter activity. ; Sixth Research Framework Programme of the European Union, Project INCA ...